The project proposed in this application combines two new fields of biomedical research and medicine: nanomedicine and vascular zip codes. Nanomedicine is a new branch of medicine that makes use of minute particles that are about the size of the smallest viruses, bigger than molecules, but much smaller than cells. The most important property of nanoparticles is that they can be engineered to perform many functions, something that cannot be achieved with a simple drug. Vascular zip codes are molecular differences in the blood vessels that can be made use of in delivering diagnostic and therapeutic agents to tumors. In this proposal, we combine expertise in different aspects of cancer nanomedicine to develop new diagnostic and treatment tools for the management of breast cancer. Dr. Tsien received the 2009 Nobel Prize in Chemistry for his work on optical probes used in cell biology research, Dr. Ruoslahti's expertise is in vascular zip codes and their use in nanoparticle targeting to tumors, and Dr. Sengupta has designed novel hybrid nanoparticles for cancer treatment. In addition, the team includes collaborators who are experts in materials science and bioengineering.

We will develop smart nanoparticles that are capable of seeking out a breast cancer and that can distinguish between premalignant lesions, fully malignant breast cancers, and metastases. We will use these probes to design a new type of a test for breast cancer and to specifically deliver anti-tumor agents to breast cancer. The test, which we have termed the "hit-and-run" test, will use bar-coded nanoparticles that are injected into the blood stream, seek out tumors, and change upon the encounter with the tumor tissue. The changes particles can then be detected in the blood. The information obtained can help determine whether a tumor is present, what stage it is, and perhaps even whether metastases are present. Importantly, the information provided by these diagnostic nanoparticles can then be used to select a nanoparticle that is best suited to deliver therapeutic compounds into the tumor of a particular patient. Few have already designed nanoparticles that simultaneously deploy combinations drugs that shut down aberrant cancer signaling pathways and predispose the tumor to chemotherapeutic drugs, which can be delivered in the same nanoparticles. Current nanoparticle drugs reach the tumor passively; our smart nanoparticles home specifically into tumors through active targeting to breast cancer zip codes. Some early generation vascular zip code probes from Dr. Ruoslahti's laboratory are in advanced clinical trials for the targeting of anticancer drugs and imaging agents. Similarly, nanoparticles from the Sengupta laboratory are being developed as clinical candidates. We expect that achieving the goals of this project will lead to the development of an advanced nanotechnology-based platform that will transform breast cancer therapy.